{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:48:56Z","timestamp":1790740136303,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endogenous agonists of the transcription factor aryl hydrocarbon receptor (AHR) such as the indolic uremic toxin, indoxyl sulfate (IS), accumulate in patients with chronic kidney disease. AHR activation by indolic toxins has prothrombotic effects on the endothelium, especially via tissue factor (TF) induction. In contrast, physiological AHR activation by laminar shear stress (SS) is atheroprotective. We studied the activation of AHR and the regulation of TF by IS in cultured human umbilical vein endothelial cells subjected to laminar fluid SS (5 dynes\/cm2). SS and IS markedly increased the expression of AHR target genes PTGS2 (encoding for COX2), AHRR, CYP1A1, and CYP1B1, as well as F3 (encoding for TF), in an AHR-dependent way. IS amplified SS-induced TF mRNA and protein expression and upregulation of AHR target genes. Interestingly, tyrosine kinase inhibition by genistein decreased SS- but not IS-induced TF expression. Finally, the increase in TF expression induced by laminar SS was not associated with increased TF activity. In contrast, IS increased TF activity, even under antithrombotic SS conditions. In conclusion, IS and SS induce AHR activation and AHR-dependent TF upregulation by different mechanisms. Impairment of the antithrombotic properties of shear stressed endothelium by toxic AHR agonists could favor cardiovascular diseases in CKD.<\/jats:p>","DOI":"10.3390\/ijms21072392","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-5799","authenticated-orcid":false,"given":"Guillaume","family":"Lano","sequence":"first","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Lafor\u00eat","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Von Kotze","sequence":"additional","affiliation":[{"name":"Centre de N\u00e9phrologie et Transplantation R\u00e9nale, AP-HM, H\u00f4pital de la Conception, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Perrin","sequence":"additional","affiliation":[{"name":"H\u00f4pital Sainte Musse, 83056 Toulon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfik","family":"Addi","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"},{"name":"D\u00e9partement de Biologie, Universit\u00e9 d\u2019Oran 1 Ahmed Benbella, LPNSA, 31000 Oran, Algerie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Brunet","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"},{"name":"Centre de N\u00e9phrologie et Transplantation R\u00e9nale, AP-HM, H\u00f4pital de la Conception, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6994-2157","authenticated-orcid":false,"given":"St\u00e9phane","family":"Poitevin","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-7884","authenticated-orcid":false,"given":"St\u00e9phane","family":"Burtey","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"},{"name":"Centre de N\u00e9phrologie et Transplantation R\u00e9nale, AP-HM, H\u00f4pital de la Conception, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4594-4676","authenticated-orcid":false,"given":"Laetitia","family":"Dou","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3390\/toxins6030934","article-title":"The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: A new concept to understand cardiovascular complications of chronic kidney disease","volume":"6","author":"Sallee","year":"2014","journal-title":"Toxins (Basel)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11508","DOI":"10.1021\/bi980087p","article-title":"Activation of the Ah receptor by tryptophan and tryptophan metabolites","volume":"37","author":"Rogers","year":"1998","journal-title":"Biochemistry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1021\/bi901786x","article-title":"The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor","volume":"49","author":"Schroeder","year":"2010","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Addi, T., Dou, L., and Burtey, S. 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